LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells

Elsa M. Reyes-Reyes; Ivan Aispuro; Marco A. Tavera-Garcia; Matthew Field; Sara Moore; Irma Ramos; Kenneth S. Ramos

doi:10.18632/oncotarget.21953

LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells

Elsa M. Reyes-Reyes, Ivan Aispuro, Marco A. Tavera-Garcia, Matthew Field, Sara Moore, Irma Ramos, Kenneth S. Ramos

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Although several lines of evidence have established the central role of epithelialto- mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE- 1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo. These findings identify a TGFβ1- LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

Original language	English (US)
Pages (from-to)	103828-103842
Number of pages	15
Journal	Oncotarget
Volume	8
Issue number	61
DOIs	https://doi.org/10.18632/oncotarget.21953
State	Published - 2017

Keywords

EMT programming
LINE-1
Oncogenesis

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.21953

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@article{381deb9adf8b406caeb8717a4754db43,

title = "LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells",

abstract = "Although several lines of evidence have established the central role of epithelialto- mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE- 1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo. These findings identify a TGFβ1- LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.",

keywords = "EMT programming, LINE-1, Oncogenesis",

author = "Reyes-Reyes, {Elsa M.} and Ivan Aispuro and Tavera-Garcia, {Marco A.} and Matthew Field and Sara Moore and Irma Ramos and Ramos, {Kenneth S.}",

note = "Funding Information: This work was supported in part by University of Arizona Health Sciences funding to KSR and University of Arizona Diversity and Inclusion Award and Career Development Award to EMRR. Publisher Copyright: {\textcopyright} Reyes-Reyes et al.",

year = "2017",

doi = "10.18632/oncotarget.21953",

language = "English (US)",

volume = "8",

pages = "103828--103842",

journal = "Oncotarget",

issn = "1949-2553",

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TY - JOUR

T1 - LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells

AU - Reyes-Reyes, Elsa M.

AU - Aispuro, Ivan

AU - Tavera-Garcia, Marco A.

AU - Field, Matthew

AU - Moore, Sara

AU - Ramos, Irma

AU - Ramos, Kenneth S.

N1 - Funding Information: This work was supported in part by University of Arizona Health Sciences funding to KSR and University of Arizona Diversity and Inclusion Award and Career Development Award to EMRR. Publisher Copyright: © Reyes-Reyes et al.

PY - 2017

Y1 - 2017

N2 - Although several lines of evidence have established the central role of epithelialto- mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE- 1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo. These findings identify a TGFβ1- LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

AB - Although several lines of evidence have established the central role of epithelialto- mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE- 1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo. These findings identify a TGFβ1- LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

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KW - LINE-1

KW - Oncogenesis

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ER -

LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells

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Keywords

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